Substance use is a leading cause of preventable death and disability. Substance use typically onsets and progresses during adolescence. Thus, identifying novel risk factors for adolescent substance use initiation and progression may inform the development of innovative preventive interventions that reduce the public health burden of substance use. Anhedonia-an affective dimension indicative of diminished interest and pleasure in rewarding-has been recently identified as a correlate of substance use. However, critical gaps in the extant literature prevent research on anhedonia's relation with substance use from having a substantial impact on the field. For example, existing research has been entirely cross-sectional and has failed to parse out the role of common antecedents and contextual factors, leaving the casual features of this association unclear. Also, past work has primarily studied adults, with only three published studies of anhedonia-substance use relations in adolescents; each of these studies are subject to critical limitations. Furthermore, each prior study has used only a single measure anhedonia based on subjective report, which ignores multi-faceted nature of the anhedonia construct. Elucidating the relative roles of distinct facets of anhedonia in substance use is critical for designing novel prevention programs that raise hedonic response to an interest in healthy alternative non-drug reinforces. Additionally, this literature has been greatly disjointed and theoretical, with no previous effort to integrate findings into a unifying model within larger conceptualization of risk. Yet, it is important for models to identify theoretial mechanisms by which anhedonia increases substance use risk in a developmental pathway from use initiation to progression in order to advance basic theory and inform intervention development. Such research is critical in order to move forward with developing substance use preventive interventions that target anhedonia. Accordingly, we propose a longitudinal study to test hypotheses based on a novel integrative model, which predicts that anhedonia gives rise to a causal risk pathway that influences both substance use initiation and progression via positive reinforcement mechanisms. This model purports that individuals with higher anhedonia have expectations that substances will produce positive effects and are willing to use substances, which could promote substance use initiation. Once use is initiated, high-anhedonia individuals may be more sensitive to the acute subjective rewarding effects of drugs, which may further devalue the relative salience of non-drug rewards and result in declining engagement in alternative reinforces. These two factors may create a strong imbalance between the value of drug-related versus alternative reinforces, which may drive motivation to use again and increase likelihood of substance use progression. These pathways may be particularly prominent for those with concomitant characteristics that facilitate the expression of anhedonia's influence on motivation to initiation and progress substance use. Once consistent use is established, repeated drug exposure may cause psychobiological adaptations that further escalate anhedonia, recapitulate this cycle, and lead to more use. In this study, we will recruit a cohort f 2007 high school students to participate in a longitudinal study with 8 semiannual waves of self-report assessment (9th - 12th grades). Assessments will take place in the school setting, which will facilitate efficient and effective data collection, and will span both self-report measures an objective behavioral measures of anhedonia. The primary aims of the study are to test the hypotheses that: (1) anhedonia will prospectively predict substance use initiation among those with no prior history of use, (2) anhedonia will prospectively predict substance use progression, and (3) Greater frequency of use will prospectively predict increases in anhedonia over time. Secondary aims will positive reinforcement mechanisms that mediate and moderate the effects of anhedonia on substance use risk that are derived from the model. The information gained from this study could be of significant value to developing novel, more effective prevention strategies that enhance experiential pleasure and positive reinforcement to prevent substance use. Such efforts could ultimately allay the substantial public health burden caused by substance use disorders. PUBLIC HEALTH RELEVANCE: This study will help determine whether adolescents who have the psychological trait of anhedonia (i.e., the tendency to not enjoy or be interested in pleasurable activities) are at greater risk for using alcohol, drugs, and tobacco during high school. The study's results could inform the development of new prevention programs that stress the importance of enhancing life pleasure to prevent substance use problems in youths. Because of the enormous health costs associated with substance use, such information could be of significant value to efforts to improve public health.